Abstract
Purpose: To investigate the anti-thrombosis and anti-tumor effect of the water extract of the caulis of Sargentodoxa cuneata (Oliv.) Rehd. et Wils. (WCSW) in rat and mouse models.Methods: WCSW extract was prepared and the main constituents were determined by high pressure liquid chromatography (HPLC). The acute toxicity of the extract was determined in mice. Platelet aggregation in rat platelet-rich plasma (PRP) was examined to evaluate the effect of the extract on platelet function. Thereafter, the cytotoxic activity of WCSW on HL60, A549, S180 and H22 cells was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vivo antitumor effect of WCSW was further evaluated on H22 cells transplanted in mice, while the expression of caspase-3, caspase-9, Bcl-2 and Bax proteins were assayed by Western blot analysis.Results: Protocatechuic acid, rhodiola glucoside and chlorogenic acid were identified as the main constituents of WCSW. Platelet aggregation was significantly inhibited by treatment with the extract at concentrations of 1, 5 and 10 mg/mL. WCSW also showed significant inhibitory effect on HL60, A549, S180 and H22 cells in vitro with half maximal inhibitory concentration (IC50 value of 321.9, 285.0, 130.3 and 76.1 μg/mL, respectively. Furthermore, WCSW exhibited obvious anti-tumor effect on H22 transplanted tumor in vivo. After treatment with WCSW, caspase-3, caspase-9 and Bax were significantly (p < 0.05) up-regulated, whereas Bcl-2 was significantly (p < 0.05) down-regulated in the tumor tissues.Conclusion: WCSW possesses significant antithrombosis and anti-tumor effect, and therefore, has the potentials to be developed into effective drugs for clinical treatment of cancer and thrombosis diseases.Keywords: Sargentodoxa cuneata, Anti-thrombosis, Anti-tumor, Platelet aggregation, Apoptosis, Caspase, Protocatechuic acid, Rhodiola glucoside, Chlorogenic acid
Highlights
Thrombus formation is a pivotal event involved in the pathogenesis of cardiovascular disease, and platelets are critical in all phases of thrombus formation [1]
Three constituents including protocatechuic acid, rhodiola glucoside and chlorogenic acid were identified by comparing their retention times and UV spectra with the corresponding reference standards
The antithrombosis effect of water extract of caulis of SRW (WCSW) were studied, and it was proved to be safe by oral administration and possessed significant inhibitory effect on adenosine diphosphate (ADP), acetylsalicylic acid (AA) and collagen induced platelet aggregation in rat Platelet-rich plasma (PRP)
Summary
Thrombus formation is a pivotal event involved in the pathogenesis of cardiovascular disease, and platelets are critical in all phases of thrombus formation [1] Antithrombotic drugs, such as adenosine diphosphate (ADP) receptor blockers, acetylsalicylic acid (aspirin), and glycoprotein (GP) IIb/IIIa antagonists are used to prevent cardiovascular disease [2]. The present research was aimed to investigate the antithrombosis and anti-tumor effect of water extract of caulis of SRW (WCSW), which may encourage the development and application of this drug. The animals were administered orally with a single dose of WCSW (10, 100, 500, 1000 and 2000 mg/kg), or distilled water for the control group. The diluted PRP was incubated at 37 °C for 5 min with different concentrations of WCSW (1, 5 and 10 mg/mL).
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